HIV Battled in a New Way
New Scientist
January 7, 2007
by Roxanne Khamsi

A new, highly sensitive test can detect tiny levels of drug-resistant HIV in the blood, say researchers. They report that the test is about 1000 times more sensitive than the current methods available for spotting drug-resistant strains. The test could help patients avoid medicines that ultimately fail to curb their HIV infection.

When drug-resistant HIV emerges within patients it can multiply unchecked and subsequently weaken the immune system, making them more prone to developing AIDS. There are about 30 well-established mutations that can make HIV resistant to one of 20 drugs used to treat this infection, according to Feng Gao at the Duke Human Vaccine Institute in Durham, North Carolina, US.

With current tests, the drug resistant strain has to reach at least 20% of the viral load in a patient before it can be detected. But Gao says that by this point the resistant strain has gained a dangerous foothold in the body. Identifying the strain earlier could help doctors know which drugs to give to keep it in check.

To do this, Gao and his colleagues developed fluorescent tags that match some of the 30 resistance-related mutations. They rooted these primers in an acrylamide gel and then placed the gel in a machine along with virus extracted from the blood of 13 HIV-infected patients. The drug-resistant viral sequences stuck to primers that glow green and these are then counted by another device.

The test can pick out a mutation, such as one at position 46 in the virus’s genetic code, for example. A mutation at position 46 makes the virus resistant to the drug indinavir. If the test revealed this mutation, doctors would know not to prescribe that drug.

Gao says the new test can detect a single mutated virus among 10,000 non-mutated viruses from a patient sample. He adds that the test has an error rate of only one in every million virus particles analysed.

High stakes

Robert Shafer of the HIV Drug Resistance Database at Stanford University in California, US, agrees there is a need for improved detection of mutant strains. “The stakes are high when a physician has to choose therapy for a patient with a drug-resistant virus,” he explains.

“The correct combination of drugs can halt virus replication and disease progression in its tracks. An incorrect combination of drugs not only enables the virus to continue to replicate but also makes a patient's virus resistant to even more drugs.”

Approximately 10% to 20% of HIV-infected people in the US and Europe carry drug-resistant strains and that percentage appears to be increasing. Shafer notes that early detection might ultimately curb the spread of drug-resistant HIV strains by reducing their presencein the population.

Duke has filed for a provisional patent on the technology, and researchers there are exploring whether they might license it to a company for development.

However, Shafer says there are major challenges that this and other methods must overcome before being widely adopted. For example, some of the mutant virus might not be detected while it hides inside cells: “Many of the deadly minor drug-resistant viruses are not in plasma but reside instead in a semi-latent form in cells, which are not present at large numbers in blood samples,” he explains.